Antimicrobial and antiviral polymeric materials

ABSTRACT

The invention provides an antimicrobial and antiviral polymeric material, having microscopic particles of ionic copper encapsulated therein and protruding from surfaces thereof.

The present invention relates to an antimicrobial and antiviralpolymeric material and to a process for preparing the same. Moreparticularly, the present invention relates to an antimicrobialpolymeric material useful as a wrapping material for agriculturalproduce, as well as to an antiviral polymeric material useful for theformation of a condom sheath, surgical tubing and surgical gloves.

A problem faced by all food exporters is the attack on the agriculturalproduce after it has been harvested by microorganisms while intransport. This is especially true when the transportation is measuredin days, weeks, or months, rather than hours. Microorganisms are knownto cause severe damage to the produce, resulting in added costs whichare passed on to the consumer. An example of this is the strawberryharvest in Israel. Every year about 50% of the harvest is lost while intransportation due to the attack of microorganisms. To date, there hasbeen no effective system developed that can effectively reduce the wasterate.

There are many wrapping materials used in food transport from burlapbags to sophisticated polymer wrappings that demonstrate qualities suchas strength, flexibility, breathability and are inexpensive. However,none to date are able to control the growth of microorganisms thatflourish in packaged, agricultural produce.

According to the present invention it has now been discovered that byadding a small percentage of Cu++ in powder form to the slurry of apolymer to be formed into a wrapping material, the package is renderedantimicrobial.

It has also been surprisingly discovered that by adding Cu++ in powderform to the slurry of a polymer to be formed into a condom there isproduced a condom which inhibits and reduces active HIV-1 in bodyfluids.

Similarly, surgical gloves and surgical tubing having antimicrobial andantiviral properties can be prepared according to the present invention.

In both WO 98/06508 and WO 98/06509 there are taught various aspects ofa textile with a full or partial metal or metal oxide plating directlyand securely bonded to the fibers thereof, wherein metal and metaloxides, including copper, are bonded to said fibers.

More specifically, in WO 98/06509 there is provided a process comprisingthe steps of: (a) providing a metallized textile, the metallized textilecomprising: (i) a textile including fibers selected from the groupconsisting of natural fibers, synthetic cellulosic fibers, regeneratedfibers, acrylic fibers, polyolefin fibers, polyurethane fibers, vinylfibers, and blends thereof, and (ii) a plating including materialsselected from the group consisting of metals and metal oxides, themetallized textile characterized in that the plating is bonded directlyto the fibers; and (b) incorporating the metallized textile in anarticle of manufacture.

In the context of said invention the term “textile” includes fibers,whether natural (for example, cotton, silk, wool, and linen) orsynthetic yarns spun from those fibers, and woven, knit, and non-wovenfabrics made of those yarns. The scope of said invention includes allnatural fibers; and all synthetic fibers used in textile applications,including but not limited to synthetic cellulosic fibers (i.e.,regenerated cellulose fibers such as rayon, and cellulose derivativefibers such as acetate fibers), regenerated protein fibers, acrylicfibers, polyolefin fibers, polyurethane fibers, and vinyl fibers, butexcluding nylon and polyester fibers, and blends thereof.

Said invention comprised application to the products of an adaptation oftechnology used in the electrolyses plating of plastics, particularlyprinted circuit boards made of plastic, with metals. See, for example,Encyclopedia of Polymer Science and Engineering (Jacqueline I.Kroschwitz, editor), Wiley and Sons, 1987, vol. IX, pp 580-598. Asapplied to textiles, this process included two steps. The first step wasthe activation of the textile by precipitating catalytic noble metalnucleation sites on the textile. This was done by first soaking thetextile in a solution of a low-oxidation-state reductant cation, andthen soaking the textile in a solution of noble metal cations,preferably a solution of Pd++ cations, most preferably an acidic PdCl₂solution. The low-oxidation-state cation reduces the noble metal cationsto the noble metals themselves, while being oxidized to a higheroxidation state. Preferably, the reductant cation is one that is solublein both the initial low oxidation state and the final high oxidationstate, for example Sn++, which is oxidized to Sn++++, or Ti+++, which isoxidized to Ti++++.

The second step was the reduction, in close proximity to the activatedtextile, of a metal cation whose reduction was catalyzed by a noblemetal. The reducing agents used to reduce the cations typically weremolecular species, for example, formaldehyde in the case of Cu++.Because the reducing agents were oxidized, the metal cations are termed“oxidant cations” herein. The metallized textiles thus produced werecharacterized in that their metal plating was bonded directly to thetextile fibers.

In WO 98/06508 there is described and claimed a composition of mattercomprising:

-   -   (a) a textile including fibers selected from the group        consisting of natural fibers, synthetic cellulosic fibers,        regenerated protein fibers, acrylic fibers, polyolefin fibers,        polyurethane fibers, vinyl fibers, and blends thereof; and    -   (b) a plating including materials selected from the group        consisting of metals and metal oxides;        the composition of matter characterized in that said plating is        bonded directly to said fibers.

Said publication also claims a composition of matter comprising:

-   -   (a) a textile including fibers selected from the group        consisting of natural fibers, synthetic cellulosic fibers,        regenerated protein fibers, acrylic fibers, polyolefin fibers,        polyurethane fibers, vinyl fibers, and blends thereof; and.    -   (b) a plurality of nucleation sites, each of said nucleation        sites including at least one noble metal;        the composition of matter characterized by catalyzing the        reduction of at least one metallic cationic species to a reduced        metal, thereby plating said fibers with said reduced metal.

In addition, said publication teaches and claims processes for producingsaid products.

A preferred process for preparing a metallized textile according to saidpublication comprises the steps of:

-   -   a) selecting a textile, in a form selected from the group        consisting of yarn and fabric, said textile including fibers        selected from the group consisting of natural fibers, synthetic        cellulosic fibers, regenerated protein fibers, acrylic fibers,        polyolefin fibers, polyurethane fibers, vinyl fibers, and blends        thereof;    -   b) soaking said textile in a solution containing at least one        reductant cationic species having at least two positive        oxidation states, said at least one cationic species being in a        lower of said at least two positive oxidation states;    -   c) soaking said textile in a solution containing at least one        noble metal cationic species, thereby producing an activated        textile; and    -   d) reducing at least one oxidant cationic species in a medium in        contact with said activated textile, thereby producing a        metallized textile.

Said publications, however, are limited to coated fibers and textilesprepared according to said processes and do not teach or suggest thepossibility of incorporating ionic copper into a polymeric slurrywhereby there are produced films and fibers having microscopic particlesof ionic copper encapsulated therein and protruding therefrom and havingantimicrobial and antiviral polymeric properties, as described andexemplified herein.

With this state of the art in mind there is now provided according tothe present invention an antimicrobial and antiviral polymeric material,having microscopic particles of ionic copper encapsulated therein andprotruding from surfaces thereof.

In another aspect of the present invention there is provided a processfor preparing an antimicrobial and antiviral polymeric material,comprising preparing a polymeric slurry, introducing an ionic copperpowder and dispersing the same in said slurry and then extruding saidslurry to form a polymeric material wherein particles of said ioniccopper are encapsulated therein and protrude from surfaces thereof.

The polymeric material of the present invention can be in the form of afilm, a fiber, or a yarn, wherein said films are used per se and saidfibers and yarns can be formed into a packaging material foragricultural products.

Said material can be made from almost any synthetic polymer, which willallow the introduction of an anionic, copper dust into its liquid slurrystate. Examples of some materials are polyamides (nylon), polyester,acrylic, polypropylene, silastic rubber and latex. When the copper dustis ground down to fine powder, e.g., a size of between 1 and 10 micronsand introduced into the slurry in small quantities, e. g., in an amountof between 0.25 and 10% of the polymer weight, it was found that thesubsequent product produced from this slurry exhibited bothantimicrobial and antiviral properties.

Unlike the fibers described, e. g. in WO 98/06508 and WO 98/06509, inwhich the fibers are coated on the outside, in the present product thepolymer has microscopic particles of ionic copper encapsulated thereinand protruding from surfaces thereof. These particles which protrudefrom the surface of the polymeric material have been shown to be active,as demonstrated by the tests set forth hereinafter.

In general, the products of the present invention are produced asfollows:

-   1. A slurry is prepared from any polymer, the chief raw material    preferably being selected from a polyamide, a polyethylene, a    polyurethane and a polyester. Combinations of more than one of said    materials can also be used provided they are compatible or adjusted    for compatibility. The polymeric raw materials are usually in bead    form and can be mono-component, bi-coponent or multi-component in    nature. The beads are heated to melting at a temperature which    preferably will range from about 120 to 180° C.-   2. At the hot mixing stage, before extrusion, a powder of ionic    copper is added to the slurry and allowed to spread through the    heated slurry. The particulate size will be preferably between 1 and    10 microns, however can be larger when the film or fiber thickness    can accommodate larger particles.-   3. The liquid slurry is then pushed with pressure through holes in a    series of metal plates formed into a circle called a spinneret. As    the slurry is pushed through the fine holes which are close    together, they form single fibers or if allowed to contact one    another, they form a film or sheath. The hot liquid fiber or film is    pushed upward with cold air forming a continuous series of fibers or    a circular sheet. The thickness of the fibers or sheet is controlled    by the size of the holes and speed at thich the slurry is pushed    through the holes and upward by the cooling air flow.-   4. In percentage mixtures of up to 10% by weight of ionic copper    dust demonstrated, no degradation of physical properties in a    polyamide slurry of the finished product. When tested, mixtures as    low as 1% still showed antimicrobial properties, as well as    surprisingly showing inhibition of HIV-1 activity.

Referring to the use of the material as a post harvest packaging system,it was found that microbes outside the package will not be able to enterthe enclosed area and that microbes inside the packet will havedifficulty in growing along the inside of the packaging material whichis usually where they incubate due to condensation within theencapsulated area.

As indicated hereinabove, the polymeric material of the presentinvention, having microscopic particles of ironic copper encapsulatedtherein, can also be utilized to manufacture disposable gloves andcondoms using a mold/form configuration.

In general, the chief raw material is concentrated and preserved naturalrubber latex. In addition such chemicals as acid, chlorine gases,alkalis, and corn/maize starch can be added, as is known in the art,however according to the present invention there is also added CU++ inpowder form.

Formers (or positive molds) are prepared through preparations that willkeep the liquid latex from sticking thereto. This is done through aseries of dips and treatments to the molds, as known per se in the art.The formers are then cleaned and dried and are dipped into a solution ofcoagulant chemicals. The coagulant forms a layer on the formers whichhelps to solidify latex when the formers are dipped into the latex tank.

The formers are dipped into the latex mixture, withdrawn therefrom andpassed through a curing oven. The gloves and/or condoms will bevulcanized as they pass through the different areas of the oven whichexpose the same to temperatures ranging from about 120 to 140° C. Thisprocess cross-links the latex rubber to impart the physical qualitiesrequired.

The difference between the normal process of manufacturing a disposableglove/condom and the process of the present invention is the addition ofthe Cu++ powder in the raw materials.

While the invention will now be described in connection with certainpreferred embodiments in the following examples and with reference tothe attached figures, so that aspects thereof may be more fullyunderstood and appreciated, it is not intended to limit the invention tothese particular embodiments. On the contrary, it is intended to coverall alternatives, modifications and equivalents as may be includedwithin the scope of the invention as defined by the appended claims.Thus, the following examples which include preferred embodiments willserve to illustrate the practice of this invention, it being understoodthat the particulars shown are by way of example and for purposes ofillustrative discussion of preferred embodiments of the presentinvention only and are presented in the cause of providing what isbelieved to be the most useful and readily understood description offormulation procedures as well as of the principles and conceptualaspects of the invention.

In the drawings:

FIG. 1 is an electron microscope photograph of a nylon fiber with copperparticles embedded therein and protruding therefrom after having beenadded to a polymeric slurry; and

FIG. 2 is a graphical representation of the inhibition of HIV-1 onsterilized pieces of latex gloves impregnated with varying amounts ofionic copper according to the present invention.

EXAMPLE 1 Preparation of Fibers

A total of 500 grams of a polyamide bi-component compound were preparedby heating the two beaded chemicals in separate baths each at 160° C.The two separate components were then mixed together and allowed to stirfor 15 minutes until the mixture appeared to be homogenous in color.

The mixed chemistry was again divided into two separate pots. In onepot, 25 grams of a mixture of CuO and Cu₂O powder was added yielding a1% mixture. In the second pot 6.25 grams of a mixture of CuO and Cu₂Owere added yielding a 0.25% mixture. In both cases, the temperature of160° C. was maintained. The compounds were stirred until they appearedhomogenous in color.

The two mixtures were run through a spinneret with holes that hieldedfibers of between 50 and 70 microns in diameter. Since the Cu++releasing powder was ground to particles of less than 20 microns noobstructions in the spinneret holes were observed. The extruded fiberswere air-cooled and spun on to cones.

The fibers were tested for biological activity.

The difference between the normal process of manufacturing any syntheticfiber and this process is the addition of the Cu++ releasing powder inthe raw materials.

EXAMPLE 2

100 μl aliquots of highly concentrated HIV-1 virus were incubated on topof the fibers for 30 minutes at 37° C. Then 10 μl of each pretreatedvirus were added to MT-2 cells (Lymphocyte Human Cell Line) cultured in1 ml media. The cells were then incubated for 5 days in a moistincubator at 37° C. and the virus infectivity and proliferation wasdetermined by measuring the amount of p24 (a specific HIV-1 protein) inthe supernatant with a commercial ELISA (Enzyme Based Immuno-absorbtionAssay) kit. The results are the average of duplicate experiments. Ascontrol for possible cytotoxicity of the CuO or Cu₂O to the cells,similar experiments were carried out as above, but the fibers wereincubated with 100 μl of natural medium that did not contain HIV-1. Nocytotoxicity was observed, i.e., none of the host cells were observed tobe killed, under the experimental conditions described above.

The following summarizes the evaluation of the capacity of the severalfibers impregnated with CuO and Cu₂O to inhibit HIV-1 proliferation intissue culture:

-   Negative control (Polymeric Fiber without CuO and Cu₂O): no    inhibition-   Positive control (CuO and Cu₂O powder): 70% inhibition-   1% CuO and Cu₂O Fiber: 26% inhibition.

EXAMPLE 3 Antifungal Susceptibility Testing

Susceptibility testing was performed as follows:

Agar formulation used for this test was chosen in accordance with NCCLSdocument M27-A: RPMI (RPG) and a buffered to pH 7.0 with 0, 165 Mmorpholinepropanesulfonic acid buffer (MOPS).

For the test, 90-mm-diameter plates containing agar at a depth of 4.0 mmwere used. For Candida albicans, Cryptococcus neoformans, micrococcus,Tinea pedis, and Tinea curpus, the inoculum was prepared from a 24 hourculture and a 48 hour culture respectively; whereas for Aspergillusfumigatus and Trichophyton mentagrophytes a five-day old culture wasused. Cell suspension was prepared in sterile 0.85% NaCl adjusted to aturbidity of a 0.5 McFarland standard. The agar surface was inoculatedby streaking a nontoxic swab dipped in a cell suspension across theentire surface of the agar in three directions.

After excess moisture was absorbed into the agar and the surface wascompletely dry, Chemtex/MTC treated fibers in a concentration range from3%-10% were applied to each plated. The plates were incubated at 35° C.and read after 24 hours, 48 hours, and 7 days. Antifungal activity ofthe treated fibers was considered positive if a zone of inhibition wasvisible underneath and surrounding the fibers.

Antibacterial Susceptibility Testing

Susceptibility testing was performed as described above for theantifungal activity with the following modifications: Mueller-Hintonagar (Difco, Detroit, Mich.) was the medium used. The pH was adjusted to7.2-7.4. The bacteria used for this study were Escherichia coli,Staphylococcus aureus, brevubacterium, acinetobacter and micrococcus.

Results

The treated fibers in a concentration range of 3-10% exhibitedcharacteristic inhibitory zone underneath and surrounding the fibers,indicating correct antifungal and antibacterial activity. The controls(untreated fibers) indicated no antifungal or antibacterial activity.

EXAMPLE 4

Fifty μl of RPMI 1640 medium, containing HIV-1 IIIB (laboratory T-tropicstrain, 0.36 pg p24 [amount of virus]), were placed on top of UVsterilized pieces of gloves. As negative control for viral activity, 50μl of medium was placed on the gloves, and as positive control, viruswas placed on a regular glove (i.e. no Cu++). The experiment was done induplicates, i.e., in each glove (different concentrations of Cu++) twoseparate drops with or without virus were placed.

After 20 minutes of incubation at room temperature, the 50 μl of dropscontaining the virus were mixed with 450 μl fresh medium (containing 10%fetal calf serum), and the mixture was added to 2×10⁵ MT-2 cells (alymphocyte cell line) in 1 ml medium (containing 10% fetal calf serum).

The virus-cell mixtures were then incubated in 24 well plates in a CO₂humidified incubator at 37° C. After 4 days of incubation the amount ofvirus present per well was quantified by a Reverse Transcriptase (RT)Assay.

RT is a key enzyme of the HIV-1, which can polymerize a DNA strand froman RNA strand. By adding radio-labeled deoxynucleotides, the amount ofnewly synthesized DNA can be quantified. The percentage of inhibition asshown in FIG. 2 was calculated by dividing the average counts per minute(CPM) obtained in each glove concentration by that obtained in theregular control glove.

As will be noted from said graph, twenty minutes of exposure ofconcentrated HIV-1 virus to the surface of a latex glove impregnatedwith 1% or more of a copper ion yielding compound at room temperatureresulted in a more than a 95% neutralization of subsequent virusinfectivity of lymphocytes (the main target of HIV-1). This resultpoints out the potential of an approach of impregnating copper into aslurry to form a glove or other item, such as a condom, to neutralizeinfectious viruses which may be found in human contaminated fluids suchas blood or sperm. It will be evident to those skilled in the art thatthe invention is not limited to the details of the foregoingillustrative examples and that the present invention may be embodied inother specific forms without departing from the essential attributesthereof, and it is therefore desired that the present embodiments andexamples be considered in all respects as illustrative and notrestrictive, reference being made to the appended claims, rather than tothe foregoing description, and all changes which come within the meaningand range of equivalency of the claims are therefore intended to beembraced therein.

1-9. (canceled)
 10. A process for preparing an antimicrobial andantiviral polymeric material containing a Cu++ releasing powder as ananti-microbial and anti-viral agent responsible for the antimicrobialand antiviral activity of the polymeric material, comprising: preparinga polymeric slurry, introducing a plurality of microscopic antimicrobialand antiviral particles to the polymeric slurry, wherein the paniclescomprise an antimicrobial and antiviral particles consisting of as Cu++releasing powder, wherein said particles are of a size less than 20microns, dispersing the particles in said slurry and then extruding saidslurry to form a polymeric material wherein said particles areincorporated in the polymeric material, wherein a portion of saidparticles in said polymeric material are exposed and protruding from thesurface of the polymeric material and release Cu⁺⁺ ions when exposed towater or water vapor to provide the antimicrobial and antiviral activityof the polymeric material.
 11. The process of claim 10, wherein theparticles are introduced into the slurry in an amount between 0.25 wt. %and 10 wt. % of the weight of the polymeric material.
 12. The process ofclaim 10, wherein the polymeric material is a fiber.
 13. The process ofclaim 10, wherein the polymeric material is a film.
 14. The process ofclaim 10, wherein the polymeric material comprises polyamide, polyester,or polypropylene.
 15. A process for preparing an antimicrobial andantiviral polymeric material containing a Cu++ releasing powder as ananti-microbial and anti-viral agent responsible for the antimicrobialand antiviral activity of the polymeric material, comprising: preparinga polymeric slurry, introducing a plurality of microscopic waterinsoluble particles into the polymeric slurry, wherein said particlescomprise an antimicrobial and antiviral agent consisting of a Cu++releasing powder, and wherein said particles have a size of less than 20microns and are introduced in an amount that is between 0.25 and 10% ofthe polymer weight, dispersing the particles in said slurry, and thenextruding said slurry to form a polymeric material, wherein saidparticles are incorporated in the polymer, and wherein a portion of saidparticles in said polymer are exposed and protruding from the surface ofthe material and release Cu++ ions when exposed to water or water vapor.16. The process of claim 15, wherein the polymer comprises polyamide,polyester, or polypropylene.
 17. A process for preparing anantimicrobial and antiviral polymeric material, comprising: preparing apolymeric slurry, introducing a Cu⁺⁺ releasing antibacterial agent andwherein said particles have a size in the range of less than 20 micronsand are introduced in an amount that is between 0.25 and 10% of thepolymer weight, dispersing the particles in said polymeric slurry, andthen extruding said slurry to form a polymeric material wherein saidparticles are incorporated in the polymer, and wherein a portion of saidparticles in said polymer are exposed and protruding from the surface ofthe material and release Cu⁺⁺ ions when exposed to water or water vapor.18. A process for preparing an antimicrobial polymeric material,comprising preparing a polymeric slurry, adding Cu-releasing copperoxide particles as an antimicrobial component, wherein said particlesare of a size of less than 20 microns and are added in an amount that isbetween 0.25 and 10% of the polymer weight, dispersing the particles insaid slurry and then extruding said slurry to form a polymeric materialwherein said particles are incorporated in the polymer, wherein aportion of said particles in said polymer are exposed and protrudingfrom the surface of the material and release Cu⁺⁺ ions when exposed towater or water vapor.
 19. The process of claim 18 wherein the polymercomprises polyamide, polyester, or polypropylene.
 20. The process ofclaim 19 wherein the polymeric material is a fiber.
 21. The process ofclaim 18 wherein the antibacterial agent consisting of cupric oxide andcuprous oxide is the source of antimicrobial activity of the polymericmaterial.